Mycobacterium abscessus
Experimental TherapeuticsEfficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ MiceMycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations of antibiotics, such as bedaquiline and imipenem, although in vitro data have questioned this combination. We report that the efficacy of bedaquiline-imipenem combination treatment relies essentially on the activity of bedaquiline in...
Mechanisms of Action: Physiological EffectsSynergistic Interactions of Indole-2-Carboxamides and β-Lactam Antibiotics against Mycobacterium abscessusNew drugs or therapeutic combinations are urgently needed against Mycobacterium abscessus. Previously, we demonstrated the potent activity of indole-2-carboxamides 6 and 12 against M. abscessus. We show here that these compounds act synergistically with imipenem and cefoxitin in vitro and...
Letter to the EditorKatG as Counterselection Marker for Nontuberculous Mycobacteria
Experimental TherapeuticsTBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessusLung disease caused by Mycobacterium abscessus is very difficult to cure, and treatment failure rates are high. The antituberculosis drug bedaquiline (BDQ) is used as salvage therapy against this dreadful disease. However, BDQ is highly lipophilic, displays a long terminal half-life, and presents a cardiotoxicity liability associated with QT interval prolongation....
Experimental TherapeuticsAssessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent ApproachMycobacterium abscessus is intrinsically resistant to most antimicrobial agents. The emerging infections caused by M. abscessus and the lack of effective treatment call for rapid attention. Here, we intended to construct a selectable marker-free autoluminescent...
Mechanisms of ResistanceDissecting erm(41)-Mediated Macrolide-Inducible Resistance in Mycobacterium abscessusMacrolides are the cornerstone of Mycobacterium abscessus multidrug therapy, despite that most patients respond poorly to this class of antibiotics due to the inducible resistance phenotype that occurs during drug treatment. This mechanism is driven by the macrolide-inducible ribosomal methylase encoded by erm(41), whose expression is activated by the...
Experimental TherapeuticsTHP-1 and Dictyostelium Infection Models for Screening and Characterization of Anti-Mycobacterium abscessus Hit Compounds!!NCR1!! presents a great challenge to antimycobacterial therapy due to its innate resistance against most antibiotics. M. abscessus is able to grow intracellularly in human macrophages, suggesting that intracellular models can facilitate drug discovery. Thus, we have developed two host cell models: human macrophages for use in a new high-content screening...
Editor's Pick CommentaryNo Amikacin, No Problem: a Successful Treatment Approach for Pediatric Otomastoiditis Due to Amikacin-Resistant Mycobacterium abscessusPediatric otomastoiditis due to Mycobacterium abscessus can be a devastating infection that presents multiple treatment challenges. Van Wijk et al. report the use of a structured approach with a standardized regimen of intravenous (i.v.), topical, and oral antibiotics and surgical intervention for four pediatric patients with multidrug-resistant...
Editor's Pick Challenging Clinical Case in Antimicrobial ResistanceSuccessful Systemic and Topical Treatment of Mycobacterium abscessus OtomastoiditisMycobacterium abscessus is an extensively drug-resistant opportunistic pathogen that can cause chronic otomastoiditis. There are no evidence-based treatment regimens for this severe infection. We treated four children with M. abscessus otomastoiditis with a structured regimen of topical imipenem and...
Experimental TherapeuticsAntimicrobial Treatment Provides a Competitive Advantage to Mycobacterium abscessus in a Dual-Species Biofilm with Pseudomonas aeruginosaThe physiological factors that contribute to Mycobacterium abscessus lung infections remain unclear. We determined whether antibiotic treatment targeting a major cystic fibrosis pathogen (i.e., Pseudomonas aeruginosa) could provide the ideal conditions for the establishment of...